Bioactive load-bearing composites

ABSTRACT

Methods of preparing bioactive composites are described. Also described are methods of molding such composites. Shaped bodies comprising bioactive composites are further described.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority to U.S. ProvisionalPatent Application Ser. No. 60/847,011, filed Sep. 25, 2006, which isherein incorporated by reference in its entirety.

FIELD OF THE INVENTION

This invention relates to the preparation of bioactive compositescomprising a polymer and a bioactive glass ceramic. The inventionfurther relates to the use of these composites in the preparation ofbiocompatible implantable materials and integral shaped bodies.

BACKGROUND OF THE INVENTION

Lower back pain may oftentimes be attributed to the rupture ordegeneration of lumbar intervertebral discs due to degenerative diskdisease, isthmic spondylolisthesis, post laminectomy syndrome,deformative disorders, trauma, tumors and the like. This pain may resultfrom the compression of spinal nerve roots by damaged discs between thevertebra, the collapse of the disc, and the resulting adverse effects ofbearing the majority of the patient's body weight through a damagedunstable vertebral joint. To remedy this, spinal implants may beinserted between the vertebral bodies to restore the joint to itsprevious height and stabilize the motion at that spinal segment.

Numerous materials have been described for the preparation of spinalimplants that possess desired mechanical and biological properties.Polyetheretherketone (PEEK) is a thermoplastic with excellent mechanicalproperties, including a Young's modulus of about 3.6 GPa and a tensilestrength of about 100 MPa. PEEK is partially crystalline, melts at about334° C., and is resistant to thermal degradation. PEEK is a biomaterialused in medical implants. For example, PEEK can be molded intopreselected shapes that possess desirable load-bearing properties. Butsuch materials are not bioactive, osteoproductive, or osteoconductive.Bioactive glasses and glass-ceramics are characterized by their abilityto form a direct bond with bone. A material based on the PEEK polymer,or similar types of polymers of the PEEK family that includes thebone-bonding properties of a bioactive glass would be desirable.

The prior art does not provide a material or a method of making thematerial which combines a biocompatible polymer such as PEEK with abioactive glass having a particle size larger than one micron.Furthermore, the art does not disclose a material or method of making abioactive implant material which combines PEEK and bioactive glass andwhich has the appropriate structural and mechanical properties towithstand the stresses necessary for use in spinal implants.

A combination of polymers including PEEK and combeite glass-ceramic, abioactive glass, has generally been described in U.S. Pat. Nos.5,681,872; 5,914,356; and 6,987,136; each of which is assigned to theassignee of the present invention and is incorporated herein byreference in its entirety. It has been discovered, however, thatconventional methods of combining PEEK and combeite, for example,combination using a twin screw extruder, result in a reaction betweenthe PEEK and the combeite glass-ceramic forming a material havingproperties that inhibit extruder functioning. In some instances, thehigh reactivity of such bioactive materials with the polymers makescombining bioactive materials, such as glass, ceramics, andglass-ceramics, with PEEK, or similar polymers of the PEEK family, achallenge using conventional processing. What is needed, therefore, is amethod of preparing a composite of PEEK and bioactive glass.

SUMMARY OF THE INVENTION

The present invention is directed to methods of preparing bioactivecomposites formed of particles of both polyetheretherketone (PEEK) andbioactive glass. Provided herein are novel methods which blend suchparticles together and then add to the blend a polar organic solvent,such as alcohol. The preferred ethyl alcohol is present when the blendis agitated by sonication, vibration or other methodologies to achievesubstantial homogeneity of the blend. The solvent is then removed, suchas in vacuo, to yield a homogeneous blend of particles ready forformation of composite shaped bodies useful for orthopedics, such as inthe preparation of spinal implants.

Control of particle sizes is preferred. Average particle sizes of fromabout 1 to about 200 microns, especially of from about 10 to about 25microns, are preferred for the bioactive glass. Combeite glass-ceramicis a preferred bioactive glass for these purposes. Amounts of bioactiveglass particles of from about 5 to about 60% by weight of the particlemixture are preferred with amounts of from about 45 to about 55% beingmore preferred. For some embodiments, PEEK particles in the same orgreater quantities by number than the bioactive glass are preferred withnumber ratios of from about 6:1 to about 10:1 being preferred.Additional materials, such as fillers, including reinforcing fibers, mayalso be included.

It is preferred that the particle blend mixed with polar organic solventcontains little or no water. Less than 5% by weight of water (in thesolvent) is preferred with less than 1% being more preferred. Solvent toparticle weight ratios of 2:1 to 10:1 are preferred. Preferred solventsare alcohols, with the medically acceptable ethanol being morepreferred.

After removal of solvent, the blend of PEEK and bioactive glassparticles is substantially homogeneous and ready for molding or otherthe formation of other shaped bodies. Application of conditions oftemperature and pressure for appropriate times gives molded, shapedbodies useful for orthopaedic, especially spinal, use. Further shapingsuch as by machining may be performed.

The present invention is also drawn to the shaped bodies and implantsprovided herein. Persons of skill in the art will appreciate that theconditions of temperature, pressure, and time will generally bedependent variables whose determination will require only routineexperimentation for any particular blend of particles and for anyparticular object to be formed. Determining such conditions to effectfusing of the PEEK particles to form the shaped bodies is well withinthe ordinary skill of those in the molding art.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A depicts a SEM (100×) of a sample of PEEK after immersion insimulated body fluid (SBF) for 1 day.

FIG. 1B depicts a SEM (1000×) of a sample of PEEK after immersion in SBFfor 1 day.

FIG. 1C depicts an energy dispersive spectroscopy (EDS) spectrum of asample of PEEK after immersion in SBF for 1 day. The spectrumcorresponds to the sample region shown in FIG. 2B.

FIG. 2A depicts a SEM (100×) of an exemplary embodiment of the presentinvention comprising PEEK and combeite glass-ceramic (50% by weight),after immersion in SBF for 1 day.

FIG. 2B depicts a SEM (1000×) of an exemplary embodiment of the presentinvention comprising PEEK and combeite glass-ceramic (50% by weight),after immersion in SBF for 1 day.

FIG. 2C depicts an EDS spectrum of an exemplary embodiment of thepresent invention comprising PEEK and combeite glass-ceramic (50% byweight), after immersion in SBF for 1 day. The spectrum corresponds tothe boxed area of FIG. 2B.

FIG. 3A depicts a SEM (100×) of a sample of PEEK after immersion insimulated body fluid (SBF) for 7 days.

FIG. 3B depicts a SEM (1000×) of a sample of PEEK after immersion in SBFfor 7 days.

FIG. 3C depicts an EDS spectrum of a sample of PEEK after immersion inSBF for 7 days. The spectrum corresponds to the sample region shown inFIG. 3B.

FIG. 4A depicts a SEM (100×) of an exemplary embodiment of the presentinvention comprising PEEK and combeite glass-ceramic (50% by weight),after immersion in SBF for 7 days.

FIG. 4B depicts a SEM (1000×) of an exemplary embodiment of the presentinvention comprising PEEK and combeite glass-ceramic (50% by weight),after immersion in SBF for 7 days.

FIG. 4C depicts an EDS spectrum of an exemplary embodiment of thepresent invention comprising PEEK and combeite glass-ceramic (50% byweight), after immersion in SBF for 7 days. The spectrum corresponds tothe boxed area of FIG. 4B.

FIG. 5A depicts a SEM (100×) of a sample of PEEK after immersion insimulated body fluid (SBF) for 14 days.

FIG. 5B depicts a SEM (1000×) of a sample of PEEK after immersion in SBFfor 14 days.

FIG. 5C depicts an EDS spectrum of a sample of PEEK after immersion inSBF for 14 days. The spectrum corresponds to the sample region shown inFIG. 5B.

FIG. 6A depicts a SEM (100×) of an exemplary embodiment of the presentinvention comprising PEEK and combeite glass-ceramic (50% by weight),after immersion in SBF for 14 days.

FIG. 6B depicts a SEM (1000×) of an exemplary embodiment of the presentinvention comprising PEEK and combeite glass-ceramic (50% by weight),after immersion in SBF for 14 days.

FIG. 6C depicts an EDS spectrum of an exemplary embodiment of thepresent invention comprising PEEK and combeite glass-ceramic (50% byweight), after immersion in SBF for 14 days. The spectrum corresponds tothe sample region shown in FIG. 6B.

FIG. 7 depicts a SEM of a cross-section of an exemplary embodiment ofthe present invention comprising PEEK and combeite glass-ceramic (50% byweight), after immersion in SBF for 14 days. The arrows demarcatedeposition of calcium phosphate along the surface of the composite.

FIGS. 8A-8E depict FTIR spectra of an exemplary embodiment of thepresent invention comprising PEEK and combeite glass-ceramic (50% byweight). FIG. 8A is an FTIR spectra taken after 1 day of immersion inSBF. FIG. 8B is an FTIR spectra taken after 3 days of immersion in SBF.FIG. 8C is an FTIR spectra taken after 7 days of immersion in SBF. FIG.8D is an FTIR spectra taken after 10 days of immersion in SBF. FIG. 8Eis an FTIR spectra taken after 14 days of immersion in SBF.

FIG. 8F is an FTIR spectrum of hydroxyapatite.

FIG. 9A is an example of one embodiment of a shaped body of the presentinvention.

FIG. 9B is an example of one embodiment of a shaped body of the presentinvention.

FIG. 9C is an example of one embodiment of a shaped body of the presentinvention.

FIGS. 10A-10C illustrate exemplary composite structures of the presentinvention. Bioactive materials are represented by filled gray circles.FIG. 10A is a representation of a cross-section of homogeneous compositestructure wherein the bioactive filler particles are roughly evenlydistributed throughout the composite. FIG. 10B is a representation of across-section of a gradient composite structure wherein the bioactivefiller particles are concentrated toward the surface of the compositeand diminish toward the interior of the composite. FIG. 10C is arepresentation of a cross-section of a composite structure with surfaceadhered bioactive layers.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

According to the present invention, methods for preparing bioactivemolding composites comprising polyetheretherketone (PEEK), or similartypes of polymers in this family, and bioactive glass are described.Also described are methods of preparing bioactive implants comprisingPEEK and bioactive glass, as well as shaped bodies for intercorporealimplantation that comprise PEEK and bioactive glass.

Preferably, medical grade PEEK is used in the present invention,although industrial-grade PEEK can also be incorporated. PEEK isavailable as a powder and a desirable PEEK material for use in thepresent invention has an average particle size of about 1 to about 200microns. PEEK material having an average particle size of about 1 toabout 400 microns is also suitable. Preferably, the PEEK material has anaverage particle size of about 10 to about 100 microns.

The bioactive glass used in the present invention may be anyalkali-containing ceramic (glass, glass-ceramic, or crystalline)material that reacts as it comes in contact with physiological fluidsincluding, but not limited to, blood and serum, which leads to boneformation. In preferred embodiments, bioactive glasses, when placed inphysiologic fluids, form an apatite layer on their surface.

Preferably, the bioactive glass comprises at least one alkali metal, forexample, lithium, sodium, potassium, rubidium, cesium, francium, orcombinations thereof. In a preferred embodiment, the bioactive glasscomprises regions of combeite crystallite morphology. Such bioactiveglass is referred to herein as “combeite glass-ceramic”. Examples ofpreferred bioactive glasses suitable for use in the present inventionare described in U.S. Pat. Nos. 5,914,356 and 5,681,872, each of whichis incorporated by reference herein in its entirety. Other suitablebioactive materials include 45S5 glass and compositions comprisingcalcium-phosphorous-sodium silicate and calcium-phosphorous silicate.Further bioactive glass compositions that may be suitable for use in thepresent invention are described in U.S. Pat. No. 6,709,744, incorporatedherein by reference. Other suitable bioactive glasses includeborosilicate, silica, and Wollastonite. Suitable bioactive glassesinclude, but are not limited to, silica-, borate-, andphosphate-containing materials. It is understood that somenon-alkali-containing bioactive glass materials are within the spirit ofthe invention. Bioactive glasses, as defined herein, do not includecalcium phosphate materials, for example, hydroxyapatite and tri-calciumphosphate.

In exemplary embodiments of the present invention, the bioactive glasspossesses osteoproductive properties. As used herein, “osteoproductive”refers to an ability to allow osteoblasts to proliferate, allowing boneto regenerate. Osteoproductive may also be defined as conducive to aprocess whereby a bioactive surface is colonized by osteogenic stemcells and which results in more rapid filling of defects than thatproduced by merely osteoconductive materials. Combeite glass-ceramic isan example of an osteoproductive material.

Preferably, the bioactive glass has an average particle size of about 1to about 400 microns. Bioactive glass may have an average particle sizeof about 1 to about 200 microns, about 1 to about 100 microns, or about10 to about 100 microns. More preferably, the bioactive glass has anaverage particle size of about 5 to about 40 microns. Most preferred arebioactive glasses having an average particle size of about 10 to about25 microns. In some embodiments, the bioactive glass has an averageparticle size of less than or about 53 microns. It is envisioned that incertain embodiments of the present invention, the bioactive particlesare nanoparticulate. In some embodiments, nanoparticulate bioactiveglass is substantially excluded. In some embodiments, the bioactiveglass has average particle sizes larger than about 500 nm. It is alsocontemplated that a blend of bioactive particles of differing averageparticle sizes may be employed.

Methods of determining particle sizes are known in the art. Some methodsinclude passing the particles through several sieves to determinegeneral particle size ranges. Other methods include laser lightscattering, and still others are known to persons skilled in the art.Determination of particle size is conveniently accomplished by sievingand such may be used here. Particle size may also be appreciated via SEMimage analysis. It will be appreciated that recitation of averages orsize ranges is not meant to exclude every particle with a slightlyhigher or lower dimension. Rather, sizes of particles are definedpractically and in the context of this invention.

According to the present invention, PEEK particles and bioactive glassparticles are blended to form a particle mixture. The blending of thebioactive component with PEEK particles may be accomplished using anymethods known in the art per se, including mixing, milling, spinning,tumbling, vibrating, or shaking. In certain embodiments, the bioactiveglass is present in an amount of about 5-60% by weight of the particlemixture. In other embodiments, the bioactive glass is present in anamount of about 45-55% by weight of the particle mixture. In otherembodiments, the bioactive glass is present in an amount of about 50% byweight of the particle mixture. In certain variations of the presentinvention, the number of PEEK particles is greater than the number ofbioactive glass particles. In other variations, the ratio of PEEKparticles to bioactive glass particles is between about 6:1 and about10:1, inclusive. In certain preferred embodiments, the particle sizeratio of PEEK particles to bioactive glass particles is about 1:1.5.

While not desiring to be bound to any particular theory, it is believedthat the combination of PEEK and bioactive glass using conventionalmethods is inhibited due to the reactivity of the surface of thebioactive glass with PEEK. In such situations, it may be desirable toprepare the bioactive component prior to its combination with PEEK, orsimilar polymers. In one embodiment, preparation of the bioactivecomponent may comprise treatment with an agent which serves to remove atleast a portion of reactive alkali which may be present at the surfaceof the bioactive particle component. Aqueous solutions, such as thosecontaining a mildly acidulating agent, may be employed for this purpose.In another embodiment, the bioactive particles can be coated with PEEKor other polymers compatible with PEEK. In yet another embodiment, atleast a portion of the surface alkali of the bioactive component may bedepleted, leached, or washed, such that the surface alkali is minimized.Such minimization can be achieved by coating, flame spheroidization, orchemical treatment. It is understood that such surface treatments serveto reduce reactivity at the surface of the bioactive component. In oneembodiment, the reactive constituent, such as alkali, for example, isreduced at the surface of the bioactive component and up to about 5 toabout 10 microns into the bioactive component. Such bioactive componentsretain bioactivity.

In certain embodiments of the present invention, the bioactive glassparticles and polymer (for example, PEEK) particles may be preparedprior to their combination. For example, the bioactive glass particlesmay be prepared by rinsing, adjusting particle size, spheroidizing,coating, and/or chemically treating. The polymer (for example, PEEK)particles may be prepared by determining particle size, particle sizedistribution, composition, molecular weight, purity, viscosity, and/orparticle shape. In certain embodiments, the combination of the preparedbioactive glass particles and the polymer (for example, PEEK) particlesmay be achieved by blending. Blending sufficient to obtain substantialhomogeneity of the mixture may be accomplished using techniques known inthe art, for example, sonicating, rolling, milling, impact milling,and/or a chemical slurry. In certain embodiments, the blending may besufficient to provide a composite having a gradient of bioactivematerial. In others, the blending may be sufficient to provide acomposite having at least one layer of bioactive material. In yetothers, the blending may be sufficient to form a coating. According tothe present invention, the blended material may be fused. Such fusionmay be accomplished using techniques known in the art, includingmolding, compacting, and/or pressure molding. Thus, provided herein is amethod of preparing a bioactive composite article comprising preparingbioactive glass particles, preparing PEEK particles, blending the PEEKparticles with the bioactive glass particles to form a particle mixture,and fusing the mixture to form the article.

In the present invention, a polar organic solvent is added to theparticle mixture. Preferably, the weight ratio of solvent to particlemixture is about 1:1 to about 4:1. Most preferably, the weight ratio ofsolvent to particle mixture is about 2:1. Certain preferred solventsinclude alcohols, for example ethanol, methanol, and isopropanol. Othersolvents include ketones, such as acetone, and halogenated solvents suchas chloroform. It is desirable that the solvent contain less than about5% by weight of water. Preferably, the solvent contains less than about1% by weight of water. Most preferably, the solvent is anhydrous.

The particle mixture and solvent is preferably agitated for a period oftime and under conditions sufficient to achieve substantial homogeneityof the mixture. In an exemplary embodiment, the mixture and solvent istumbled on rollers for about one to about two hours. As used herein,“homogeneity” and “homogeneous” describe a composition that issubstantially uniform in structure and/or composition throughout. Theagitation may comprise sonication or mechanical vibration, or both. Theagitation may further comprise stirring. The term “substantiallyhomogeneous” is to be understood within the context of the invention andis not to be taken as an absolute.

In the present invention, substantially all of the solvent is removedfrom the mixture. Methods of removing solvent are known in the art perse. In certain embodiments, the solvent can be removed under reducedpressure. In other embodiments, the solvent can be removed byevaporation. The mixture may optionally be re-blended to further ensurehomogeneity. For example, the dried powder may be tumbled for about oneto about two hours on rollers.

Also in accordance with the present invention, at least one filler maybe added to the mixture of polymer and bioactive glass. Such fillers cancomprise, at least partially, reinforcing fibers. Examples of preferredfillers include carbon, glass, radiopaque material, barium glass,resorbable material, or mixtures thereof. In certain embodiments, thefiller may comprise calcium phosphate having macro-, meso-, andmicroporosity. More preferably, the porosity of the calcium phosphate isinterconnected. The preparation of preferred forms of calcium phosphatefor use in the present invention is described in U.S. Pat. Nos.6,383,519 and 6,521,246, incorporated herein by reference in theirentireties. An exemplary calcium phosphate product is Vitoss® ScaffoldSynthetic Cancellous Bone Void Filler (Orthovita, Inc., Malvern, Pa.).

In accordance with the present invention, the steps described forpreparing the bioactive composite may be repeated to achieve substantialhomogeneity of the composite.

Having prepared the bioactive particle composite according to themethods described herein, the composite can be molded using conventionalmolding techniques to form an integral shaped bioactive implant body,such as those shown in FIGS. 9A-9C. Alternatively, the composite may bemolded such that after further machining, a shaped body for implantationis prepared. For example, the composite may be molded to form a genericshape, for example a cylinder or block, which is then machined to apre-selected implant shape. A mold can be filled with the composite andpressure, for example about 2 to about 80 MPa, can be applied to form abioactive implant or a generic shape suitable for further machining.Heat sufficient to melt at least one component of the composite can alsobe used. In addition to using heat to melt at least one component of thecomposite, vibrational, radiofrequency, or microwave energy, orcombinations thereof, can be used to melt at least one component of thecomposite.

Once the bioactive spinal implant has been molded, treatment of theimplant can be performed to alter the mechanical properties of thecomposite. For example, after molding, the implant can be held at atemperature above room temperature for a period of time. In otherinstances, the molded implant can be cooled to room temperature or belowby, for example, immersion in water or liquid nitrogen.

Once the composite has been molded into a desired shaped body,conventional finishing techniques may be employed, such as milling,cutting, drilling, and/or sanding of the shaped body.

Composite structures contemplated by the present invention includehomogeneous composites prepared by blending PEEK, or a related polymer,with bioactive glass, using the methods described herein. Also withinthe scope of the present invention are composites comprising a gradientof bioactive material. For example, the gradient can vary along one ormore dimensions. In another example, there may be greater concentrationsof bioactive material in one or more portions of the composite ascompared with other portions. Also envisioned are composites comprisinglayers of one or more types or concentrations of bioactive material, solong as at least one layer is in accordance with the invention.Structures prepared from such composites may have a bioactive portion ofthe composite at one or more specific locations, such that the bioactivematerial occurs where design specifications call for bone bonding. Inother embodiments, structures prepared using the composites of thepresent invention may have bioactive materials adhered to the surface.In further embodiments of the present invention, the structures may becoated with materials described herein and such coatings may be usefulon metals, polymeric, or ceramic intracorporeal implants.

Composites and shaped bodies of the present invention preferablydemonstrate load-bearing and mechanical properties suitable for use inspinal implants. Composites and shaped bodies of the present inventionalso preferably demonstrate bioactivity. As used herein, “bioactive”relates to the chemical formation of a calcium phosphate layer(amorphous, partially crystalline, or crystalline) via ion exchangebetween surrounding fluid and the composite material. “Bioactive” alsopertains to materials that, when subjected to intracorporealimplantation, elicit a reaction. Such a reaction leads to boneformation, attachment into or adjacent to implants, and/or boneformation or apposition directly to the implants, usually withoutintervening fibrous tissue. Referring to FIGS. 1-8, a composite,comprising PEEK and 50% by weight of combeite glass-ceramic (having <53micron average particle size), was prepared using the methods set forthherein. In vitro bioactivity studies were performed with the composites,prepared as described herein, using the method of Kokubo, How useful isSBF is predicting in vivo bone bioactivity, Biomaterials (2006)27:2907-2915. After immersion in simulated body fluid (SBF) for 1 day,the formation of calcium phosphate can be observed (FIGS. 2A-2C). Bycomparison, a sample of PEEK, without the bioactive component, immersedin SBF for 1 day, does not result in the formation of calcium phosphate(FIGS. 1A-1C). After 7 days of immersion in SBF, increasing amounts ofcalcium phosphate formation can be observed in the composite (FIGS.4A-4C), whereas no calcium phosphate formation is observed in the PEEKsample (FIGS. 3A-3C). After 14 days of immersion in SBF, calciumphosphate can still be observed in the composite sample (FIGS. 6A-6C),but no calcium phosphate formation is observed in the PEEK sample (FIGS.5A-5C). A cross section of a composite sample which had been immersed inSBF is shown in FIG. 7. As denoted by arrows, calcium phosphateformation is observed on the surface of the composite material. Thedistribution of bioactive glass within the sample can also beappreciated in this view.

FIGS. 8A-8E are fourier transform infrared (FTIR) spectra of compositescomprising PEEK and 50% by weight of combeite glass-ceramic, preparedusing the methods set forth herein. As can be seen, characteristic peaksfor calcium phosphate (1000, 600, and 560 cm⁻¹, see FIG. 8F) increaseover time, indicative of bioactivity and progression to a maturecrystalline hydroxyapatite. Thus, an embodiment of the present inventionis a composite comprising PEEK and bioactive glass wherein the compositeis bioactive.

The following examples are set forth to further describe the inventionand are not intended to be limiting.

Example 1

1500 grams of PEEK powder (GoodFellow Corp., Devon, Pa. nominal 80micron) and 1500 grams of combeite glass-ceramic (Orthovita, Inc.,Malvern, Pa., average particle size<53 micron, non-silanated) werecombined in a polyethylene bottle and tumbled on rollers for about 1 to2 hours. Anhydrous ethanol (2:1, ethanol:powder mixture) was added andthe resulting mixture was sonicated in a glass beaker for about 5minutes while stirring. The excess alcohol was decanted and the mixturewas transferred to a glass tray and dried at about 70° C. for about 12hours. The mixture was then transferred to a polyethylene bottle andtumbled on rollers for about 1 to 2 hours.

Example 2

The material obtained from Example 1 was loaded into a stainless steelmold. A piston was inserted and about 80 MPa of pressure was applied.The mold was heat pressurized to above 340° C. and was held until thematerial melted. The mold was then held at 270° C. for about 4 hoursbefore being cooled to room temperature. After cooling, the moldedarticle was removed from the mold and milled.

Example 3

The material obtained from Example 1 was loaded into a stainless steelmold. A piston was inserted and about 80 MPa of pressure was applied.The mold was heat pressurized to above 340° C. and was held until thematerial melted. The mold was then cooled to room temperature and themolded article was removed from the mold and milled.

Those skilled in the art will appreciate that numerous changes andmodifications can be made to the many embodiments of the invention andthat such changes and modifications can be made without departing fromthe spirit of the invention. It is therefore intended that the appendedclaims cover all such equivalent variations as falling within the truespirit and scope of the invention.

1. A method of preparing a bioactive composite comprising: (a) blendingpolyetheretherketone particles and bioactive glass particles to form aparticle mixture; (b) adding a polar organic solvent to the particlemixture to form a weight ratio of solvent to particle mixture of about1:1 to about 4:1; (c) agitating the mixture for period of time and underconditions sufficient to achieve substantial homogeneity of the mixture;and (d) removing substantially all of the solvent from the mixture. 2.The method of claim 1 wherein the bioactive glass has an averageparticle size of about 1 to about 100 microns.
 3. The method of claim 1wherein the bioactive glass has an average particle size of about 10 toabout 25 microns.
 4. The method of claim 1 wherein the bioactive glassis present in an amount of about 5-60% by weight of the particlemixture.
 5. The method of claim 1 wherein the bioactive glass comprisescombeite glass-ceramic.
 6. The method of claim 1 wherein thepolyetheretherketone has an average particle size of about 1 to about400 microns in diameter.
 7. The method of claim 1 wherein the compositeis osteoproductive.
 8. The method of claim 1 wherein the bioactive glasscomprises an alkali metal.
 9. The method of claim 1 wherein thebioactive glass is present in an amount of about 5-60% by weight of theparticle mixture.
 10. The method of claim 1 wherein the number ofpolyetheretherketone particles is greater than the number of bioactiveglass particles.
 11. The method of claim 1 wherein the ratio ofpolyetheretherketone particles to bioactive glass particles is betweenabout 6:1 to about 10:1.
 12. The method of claim 1 wherein the particlesize ratio of polyetheretherketone particles to bioactive glassparticles is about 1:1.5.
 13. The method of claim 1 further comprisingmixing at least one filler with the polyetheretherketone and thebioactive glass.
 14. The method of claim 1 wherein the solvent containsless than about 5% by weight of water.
 15. The method of claim 1 whereinthe ratio of solvent to particle mixture is about 2:1.
 16. The method ofclaim 1 wherein the solvent is alcohol.
 17. The method of claim 1further comprising blending the mixture until it is substantiallyhomogeneous.
 18. The method of claim 1 wherein the composite isbioactive in vitro.
 19. A method of preparing a bioactive implantcomprising: (a) blending polyetheretherketone particles and bioactiveglass particles to form a particle mixture; (b) adding a nonaqueous,polar organic solvent to the particle mixture to form a weight ratio ofsolvent to particle mixture of about 1:1 to about 4:1; (c) agitating themixture for a time and under conditions sufficient to achievesubstantial homogeneity of the mixture; (d) removing substantially allof the solvent from the mixture; and (e) shaping said mixture underconditions of heat and pressure sufficient to provide an integral shapedbody.
 20. The method of claim 19 wherein the molding comprises heatingto a temperature sufficient to melt at least one component of themixture.
 21. The method of claim 19 wherein the molding comprisesapplying pressure.
 22. The method of claim 19 further comprising holdingthe mixture for a time and at a temperature sufficient to effect curing.23. The method of claim 19 further comprising cooling the implant. 24.The method of claim 19 further comprising cooling the implant to at orbelow ambient temperature.
 25. A shaped body for spinal implantationcomprising: a shaped, substantially homogeneous mixture ofpolyetheretherketone and bioactive glass prepared from a blend ofpolyetheretherketone particles and bioactive glass ceramic particlesformed into a particle mixture to which a polar organic solvent has beenadded to form a weight ratio of solvent to particle mixture of about 1:1to about 4:1; the mixture having been agitated for a time and underconditions sufficient to achieve substantial homogeneity of the mixture;substantially all of the solvent having been removed from the particlemixture; and, the shaped mixture having been cured under conditions ofheat, time and pressure sufficient to harden the body.
 26. A method ofpreparing a bioactive composite comprising: (a) preparing a bioactiveglass to minimize alkali surface reactivity; (b) blendingpolyetheretherketone particles and the bioactive glass to form aparticle mixture; (c) adding a polar organic solvent to the particlemixture to form a weight ratio of solvent to particle mixture of about1:1 to about 4:1; (d) agitating the mixture for a period of time andunder conditions sufficient to achieve substantial homogeneity of themixture; and (e) removing substantially all of the solvent from themixture.
 27. A composite material suitable for use in spinal implantsproduced by the method of claim
 1. 28. The composite material of claim27 wherein said material is bioactive in vitro.
 29. The compositematerial of claim 27 wherein the bioactive glass has an average particlesize of about 10 to about 100 microns.
 30. A bioactive compositecomprising polyetheretherketone and bioactive glass, wherein thebioactive glass has a particle size range from 1 to 400 microns, andwherein the bioactive glass comprises from 5% to 60% by weight of thecomposite.
 31. A bioactive composite of claim 30, wherein thepolyetheretherketone has a particle size range from 1 to 400 micronsprior to formation of said composite.
 32. The bioactive composite ofclaim 30, wherein the bioactive glass is combeite having a particle sizerange from 1 to 200 microns.
 33. The bioactive composite of claim 30,wherein the bioactive glass is combeite having a particle size rangefrom about 90 to 150 microns.
 34. The bioactive composite of claim 30,wherein the bioactive glass is combeite having a particle size of lessthan 53 microns.
 35. The bioactive composite of claim 30, wherein thebioactive glass comprises from 45% to 55% by weight of the composite.36. The bioactive composite of claim 30, wherein the bioactive glassfurther comprises at least one alkali metal.
 37. The bioactive compositeof claim 30, wherein the composite further comprises a filler.
 38. Thebioactive composite of claim 37, wherein the filler is at least oneselected from the group consisting of a reinforcing fiber, carbon,glass, a radiopaque material, barium glass, a resorbable material. 39.The bioactive composite of claim 37, wherein the filler is a calciumphosphate material.
 40. A bioactive composite comprisingpolyetheretherketone and combeite prepared by combiningpolyetheretherketone having a particle size range from 1 to 400 micronswith combeite having a particle size range from 1 to 400 microns,wherein the combeite comprises between about 5% to about 60% by weightof the composite.
 41. The bioactive composite of claim 40, wherein thecombeite comprises from 20% to 40% by weight of the composite.
 42. Ashaped body for intracorporeal implantation comprising the bioactivecomposite of claim
 30. 43. A intracorporeal implant comprising thebioactive composite of claim
 30. 44. A spinal implant comprising thebioactive composite of claim 30.